CN105770866A - Slow-release medicine composition for reducing blood sugar and preparation method thereof - Google Patents
Slow-release medicine composition for reducing blood sugar and preparation method thereof Download PDFInfo
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- CN105770866A CN105770866A CN201610217489.7A CN201610217489A CN105770866A CN 105770866 A CN105770866 A CN 105770866A CN 201610217489 A CN201610217489 A CN 201610217489A CN 105770866 A CN105770866 A CN 105770866A
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- medicine composition
- spacetabs type
- hypoglycemic medicine
- blood sugar
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- 239000003814 drug Substances 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000008280 blood Substances 0.000 title abstract description 25
- 210000004369 blood Anatomy 0.000 title abstract description 25
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 28
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 28
- 239000000017 hydrogel Substances 0.000 claims abstract description 28
- 239000003755 preservative agent Substances 0.000 claims abstract description 21
- 230000002335 preservative effect Effects 0.000 claims abstract description 21
- QBDCOUHKEVYWLO-UHFFFAOYSA-N Decanoyl acetaldehyde Chemical compound CCCCCCCCCC(=O)CC=O QBDCOUHKEVYWLO-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920002101 Chitin Polymers 0.000 claims abstract description 18
- 102000030595 Glucokinase Human genes 0.000 claims abstract description 18
- 108010021582 Glucokinase Proteins 0.000 claims abstract description 18
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 claims abstract description 15
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 claims abstract description 15
- 229920002079 Ellagic acid Polymers 0.000 claims abstract description 15
- 235000010469 Glycine max Nutrition 0.000 claims abstract description 15
- 229960002852 ellagic acid Drugs 0.000 claims abstract description 15
- 235000004132 ellagic acid Nutrition 0.000 claims abstract description 15
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 15
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 15
- 244000068988 Glycine max Species 0.000 claims abstract description 14
- 229940078480 calcium levulinate Drugs 0.000 claims abstract description 12
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims abstract description 12
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims abstract description 6
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- -1 Polyethylene Polymers 0.000 claims description 22
- 241001597008 Nomeidae Species 0.000 claims description 19
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 17
- 229930182832 D-phenylalanine Natural products 0.000 claims description 17
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 17
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 17
- 229920000615 alginic acid Polymers 0.000 claims description 15
- 235000010443 alginic acid Nutrition 0.000 claims description 15
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 claims description 13
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 claims description 13
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims description 10
- 235000020778 linoleic acid Nutrition 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 229920001577 copolymer Polymers 0.000 claims description 9
- 239000004698 Polyethylene Substances 0.000 claims description 8
- 229920000573 polyethylene Polymers 0.000 claims description 8
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical group C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 claims description 7
- 229960000698 nateglinide Drugs 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 5
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical group [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 5
- 235000010234 sodium benzoate Nutrition 0.000 claims description 5
- 239000004299 sodium benzoate Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 229920001451 polypropylene glycol Polymers 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 9
- 230000007774 longterm Effects 0.000 abstract description 9
- 230000009471 action Effects 0.000 abstract description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000036039 immunity Effects 0.000 abstract description 2
- FVXDCNFHHUUREB-UHFFFAOYSA-N (7Z,10Z,13Z,16Z)-1-amino-2-hydroxydocosa-7,10,13,16-tetraen-3-one Chemical compound C(CCCC=C/CC=C/CC=C/CC=C/CCCCC)(=O)C(O)CN FVXDCNFHHUUREB-UHFFFAOYSA-N 0.000 abstract 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 abstract 1
- 125000001711 D-phenylalanine group Chemical class [H]N([H])[C@@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- 241000414067 Inonotus obliquus Species 0.000 abstract 1
- 150000002632 lipids Chemical class 0.000 abstract 1
- 235000010413 sodium alginate Nutrition 0.000 abstract 1
- 229940005550 sodium alginate Drugs 0.000 abstract 1
- 239000000661 sodium alginate Substances 0.000 abstract 1
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 206010018473 Glycosuria Diseases 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 230000002612 cardiopulmonary effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000857 drug effect Effects 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 229940040102 levulinic acid Drugs 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 230000000291 postprandial effect Effects 0.000 description 4
- 229920000881 Modified starch Polymers 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 3
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 3
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 239000007935 oral tablet Substances 0.000 description 3
- 229940096978 oral tablet Drugs 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002641 glycemic effect Effects 0.000 description 2
- 230000012447 hatching Effects 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 150000003587 threonine derivatives Chemical class 0.000 description 2
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- GRWCNLYJHUHBOD-XVSDJDOKSA-N 2-hydroxyethylazanium;(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate Chemical compound [NH3+]CCO.CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O GRWCNLYJHUHBOD-XVSDJDOKSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 150000001294 alanine derivatives Chemical class 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
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- 238000013270 controlled release Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 210000001508 eye Anatomy 0.000 description 1
- 235000021472 generally recognized as safe Nutrition 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/121—Ketones acyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/01—Phosphotransferases with an alcohol group as acceptor (2.7.1)
- C12Y207/01002—Glucokinase (2.7.1.2)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a slow-release medicine composition for reducing blood sugar and a preparation method thereof. The composition is mainly prepared from, by weight, 80-200 parts of a biodegradable polymer, 30-70 parts of thermosensitive hydrogel, 3-10 parts of a D-phenylalanine derivative, 2-10 parts of glucokinase, 5-12 parts of sodium alginate, 3-20 parts of inonotus obliquus, 5-20 parts of a chitin derivative, 1-6 parts of ellagic acid, 1-5 parts of linoleic acid, 5-20 parts of soybean oligosaccharide, 2-8 parts of arachidonoylet-hanolamine, 3-10 parts of calcium levulinate, 1-4 parts of houttuynin and 0.2-1 part of a preservative. The slow-release medicine composition for reducing blood sugar can effectively improve the blood sugar control condition of a patient suffering from type 2 diabetes, the medicine can be stably released for a long term, proper concentration and action time of the medicine can be kept in the body, and the taking frequency and dosage of the medicine can be reduced; besides, blood lipid can be reduced, the immunity of the patient can be enhanced, a too small weight caused by diabetes is prevented, and the slow-release medicine composition for reducing blood sugar is beneficial to long-term blood sugar control.
Description
Technical field
The present invention relates to diabetic technical field, be specifically related to a kind of spacetabs type hypoglycemic medicine composition
And preparation method thereof.
Background technology
Diabetes are the chronic diseases being characterized with elevated blood glucose levels, are segmented into two types: I type glycosuria
Disease, it causes pancreas to stop producing insulin, and type ii diabetes, and it also results in insulin resistant increases
Degenerate with pancreas Instreptozotocin Induced.Hyperglycemia is then owing to defect of insulin secretion or its biological agent are impaired,
Or both have concurrently and cause.Long-standing hyperglycemia during diabetes, causes various tissue, particularly eye, kidney,
Heart, blood vessel, neural chronic lesion, dysfunction.China has more than 92,000,000 adults and suffers from glycosuria
Disease, also 1.5 hundred million people are the potential patients of diabetes, i.e. just have 1 to suffer from every about in 10 adults
Diabetes.Gliclazide is 2nd generation sulphanylureas oral antidiabetic drug, and such medicine is that generally recognized as safe is effective in the world
Oral hypoglycaemic medicine, for the routine administration of type Ⅱdiabetes mellitus of growing up at present, diabetes can occur multiple also
Sending out disease, some the most directly threatens the life of patient.Type Ⅱdiabetes mellitus generation cardiovascular disease and the danger of apoplexy
Dangerous exceeding 2-4 times than general population, therefore patient can reduce life-span 5-10.At all and glycosuria
In sick relevant death, having about 80% relevant with cardiovascular disease (CVD), therefore, medical circle is the most all
Take all necessary measure energetically, try one's best and reduce the factor of type Ⅱdiabetes mellitus cardiovascular danger.
At present, having much as therapeutic type diabetes medicament, the defect generally existed is exactly duration of efficacy
Short, bioavailability is relatively low, and domestic demand was repeatedly taken medicine on 1st.
Summary of the invention
Present invention solves the technical problem that and be to provide a kind of spacetabs type hypoglycemic medicine composition and preparation method thereof,
The glycemic control situation of patients with NIDDM can be effectively improved, reduce access times and the dosage of medicine,
Long-term control blood glucose there is certain benefit.
The technical scheme is that a kind of spacetabs type hypoglycemic medicine composition, by weight, mainly
It is composed of the following components in parts by weight: biodegradable polymers 80-200 part, temperature-sensitive hydrogel 30-70
Part, D-phenylalanine derivant 3-10 part, glucokinase 2-10 part, Algin 5-12 part, Pyropolyporus fomentarius (L.ex Fr.) Teng hole
Bacterium 3-20 part, chitin derivativ 5-20 part, ellagic acid 1-6 part, linoleic acid 1-5 part, Semen sojae atricolor are low
Polysaccharide 5-20 part, anandamide 2-8 part, calcium levulinate 3-10 part, houttuynine sodium bisulfite 1-4 part,
Preservative 0.2-1 part.
Further, in such scheme, described biodegradable polymers is handed over for the Polyethylene Glycol that methylates-second
Ester-lactide copolymer.The monomer molar ratio of the described Polyethylene Glycol-glycolide-lactide copolymer that methylates
In the range of 50: 45-20: 60, molecular weight is 10000-50000 dalton.Can be in physiological conditions
Can degrade voluntarily, collapse or metabolism, make medicine keep suitable concentration and action time in vivo.
Further, described temperature-sensitive hydrogel is selected from poly(ethylene oxide) or poly(propylene oxide), can reach long
The release medicine that phase is stable, good biocompatibility, can degrade voluntarily.
Further, described D-phenylalanine derivant is selected from Nateglinide, is a kind of novel mealtime blood sugar
Regulator, can effectively control level of postprandial blood sugar, is difficult to cause cardiovascular side effects, hypoglycemic incidence rate
Relatively low.
Further, described chitin derivativ is oligochitosan, to the immunomodulating of human body, antitumor, fall
Blood fat, regulate blood glucose, improve liver and cardio-pulmonary function and other different physiological roles important roles.
Further, described preservative is sodium benzoate, prevents medicine putrid and deteriorated, extends EDD,
Ensure drug effect.
A kind of spacetabs type hypoglycemic medicine composition, its preparation method is:
(1) by described proportioning take biodegradable polymers 80-200 part, temperature-sensitive hydrogel 30-70 part,
D-phenylalanine derivant 3-10 part, glucokinase 2-10 part, Algin 5-12 part, Inonqqus obliquus
3-20 part, chitin derivativ 5-20 part, ellagic acid 1-6 part, linoleic acid 1-5 part, soy oligosaccharides
Sugar 5-20 part, anandamide 2-8 part, calcium levulinate 3-10 part, houttuynine sodium bisulfite 1-4 part,
Preservative 0.2-1 part is standby；
(2) described temperature-sensitive hydrogel is dissolved completely in normal saline, is then heated to 50 DEG C
Place into after keeping 15-20 minute in 0 DEG C of frozen water and hatch until forming water white solution；
(3) described biodegradable polymers is disperseed in deionized water, be added dropwise to the nothing of step (2)
Color clear solution, add described D-phenylalanine derivant, glucokinase, Algin, Inonqqus obliquus,
Chitin derivativ, ellagic acid, linoleic acid, soybean oligo saccharide, anandamide, levulinic acid
Calcium, houttuynine sodium bisulfite, preservative, stirring, form mixed solution, ultrasonic reaction 10-under normal pressure, room temperature
30min, at normal pressure, stands 3-10h at 5-20 DEG C, is evaporated to water content less than 40-45%, i.e. obtains
Described spacetabs type hypoglycemic medicine composition.
Further, the consumption of described normal saline is 6-11 times of weight of described temperature-sensitive hydrogel.
Further, the consumption of described deionized water reaches with the concentration sum of described biodegradable polymers
100-450g/L is limited.
The invention has the beneficial effects as follows: the spacetabs type hypoglycemic medicine composition of the present invention, it is possible to be effectively improved II
The glycemic control situation of diabetes mellitus type, common by biodegradable polymers and temperature-sensitive hydrogel
Effect, can reach release medicine steady in a long-term, when making medicine keep suitable concentration and effect in vivo
Between, and both ingredients Biogenic compatibilitys are good, can degrade the most voluntarily, collapse or metabolism,
Reduce the access times of medicine and dosage, and can blood fat reducing, strengthen the immunity of patient, prevent glycosuria
The excess weight that disease causes is relatively light, and long-term control blood glucose is had certain benefit.
Detailed description of the invention
Embodiment 1:
A kind of spacetabs type hypoglycemic medicine composition, by weight, is mainly grouped by the one-tenth of following weight portion
Become: biodegradable polymers 80 parts, temperature-sensitive hydrogel 30 parts, D-phenylalanine derivant 3 parts,
Glucokinase 2 parts, Algin 5 parts, Inonqqus obliquus 3 parts, chitin derivativ 5 parts, ellagic acid 1
Part, linoleic acid 1 part, soybean oligo saccharide 5 parts, anandamide 2 parts, calcium levulinate 3 parts,
Houttuynine sodium bisulfite 1 part, preservative 0.2 part.
Wherein, described biodegradable polymers is the Polyethylene Glycol-glycolide-lactide copolymer that methylates.
The monomer molar ratio of the described Polyethylene Glycol-glycolide-lactide copolymer that methylates is in the range of 50: 45:
60, molecular weight is 10000 dalton, it is possible to can degrade voluntarily in physiological conditions, collapse or metabolism,
Medicine is made to keep suitable concentration and action time in vivo.Described temperature-sensitive hydrogel is poly(ethylene oxide),
Release medicine steady in a long-term, good biocompatibility can be reached, can degrade voluntarily.Described D-phenylalanine
Derivant is selected from Nateglinide, is a kind of novel blood sugar regulator used during user having meals, can effectively control post-prandial glycemia water
Flat, it is difficult to cause cardiovascular side effects, hypoglycemic incidence rate is relatively low.Described chitin derivativ is that shell is few
Sugar, to immunomodulating, antitumor, blood fat reducing, the regulation blood glucose of human body, improve liver and cardio-pulmonary function and
Other different physiological roles important roles.Described preservative is sodium benzoate, prevents medicine putrid and deteriorated,
Extend EDD, it is ensured that drug effect.
A kind of spacetabs type hypoglycemic medicine composition, its preparation method is:
(1) biodegradable polymers 80 parts, temperature-sensitive hydrogel 30 parts, D-phenylpropyl alcohol are taken by described proportioning
Threonine derivative 3 parts, glucokinase 2 parts, Algin 5 parts, Inonqqus obliquus 3 parts, chitin are derivative
Thing 5 parts, ellagic acid 1 part, linoleic acid 1 part, soybean oligo saccharide 5 parts, anandamide 2
Part, calcium levulinate 3 parts, houttuynine sodium bisulfite 1 part, preservative 0.2 part, standby；
(2) being dissolved completely in normal saline by described temperature-sensitive hydrogel, the consumption of described normal saline is
6 times of the weight of described temperature-sensitive hydrogel, place into 0 DEG C after being then heated to 50 DEG C of holdings 15 minutes
In frozen water, hatching is until forming water white solution；
(3) by described biodegradable polymers disperse in deionized water, the consumption of described deionized water with
The concentration sum of described biodegradable polymers reaches 100g/L and is limited, and is added dropwise to the colourless of step (2)
Clear solution, add described D-phenylalanine derivant, glucokinase, Algin, Inonqqus obliquus,
Chitin derivativ, ellagic acid, linoleic acid, soybean oligo saccharide, anandamide, levulinic acid
Calcium, houttuynine sodium bisulfite, preservative, stirring, form mixed solution, ultrasonic reaction under normal pressure, room temperature
10min, at normal pressure, stands 3h at 5 DEG C, is evaporated to water content less than 40%, i.e. obtains described slow release
Type hypoglycemic medicine composition；
(4) this spacetabs type hypoglycemic medicine composition will be proportionally added into adjuvant: the pregelatinized Starch of 15%, 2%
Hydroxymethyl cellulose, the hydrogenated vegetable oil etc. of 0.02%, by mixing, granulate, be dried, pelletize, tabletting
It is prepared as oral tablet etc. technique.
Embodiment 2:
A kind of spacetabs type hypoglycemic medicine composition, by weight, is mainly grouped by the one-tenth of following weight portion
Become: biodegradable polymers 140 parts, temperature-sensitive hydrogel 5 parts, D-phenylalanine derivant 6.5 parts,
Glucokinase 6 parts, Algin 8.5 parts, Inonqqus obliquus 11.5 parts, chitin derivativ 12.5 parts,
Ellagic acid 3.5 parts, linoleic acid 3 parts, soybean oligo saccharide 12.5 parts, anandamide 5 parts,
Calcium levulinate 6.5 parts, houttuynine sodium bisulfite 2.5 parts, preservative 0.6 part.
Wherein, described biodegradable polymers is the Polyethylene Glycol-glycolide-lactide copolymer that methylates.
The monomer molar ratio of the described Polyethylene Glycol-glycolide-lactide copolymer that methylates is in the range of 50: 32.5:
60, molecular weight is 30000 dalton, it is possible to can degrade voluntarily in physiological conditions, collapse or metabolism,
Medicine is made to keep suitable concentration and action time in vivo.Described temperature-sensitive hydrogel is poly(propylene oxide),
Release medicine steady in a long-term, good biocompatibility can be reached, can degrade voluntarily.Described D-phenylalanine
Derivant is selected from Nateglinide, is a kind of novel blood sugar regulator used during user having meals, can effectively control post-prandial glycemia water
Flat, it is difficult to cause cardiovascular side effects, hypoglycemic incidence rate is relatively low.Described chitin derivativ is that shell is few
Sugar, to immunomodulating, antitumor, blood fat reducing, the regulation blood glucose of human body, improve liver and cardio-pulmonary function and
Other different physiological roles important roles.Described preservative is sodium benzoate, prevents medicine putrid and deteriorated,
Extend EDD, it is ensured that drug effect.
A kind of spacetabs type hypoglycemic medicine composition, its preparation method is:
(1) biodegradable polymers 140 parts, temperature-sensitive hydrogel 5 parts, D-phenylpropyl alcohol are taken by described proportioning
Threonine derivative 6.5 parts, glucokinase 6 parts, Algin 8.5 parts, Inonqqus obliquus 11.5 parts, carapace
Element derivant 12.5 parts, ellagic acid 3.5 parts, linoleic acid 3 parts, soybean oligo saccharide 12.5 parts, Semen arachidis hypogaeae
Tetraenoic acid ethanolamine 5 parts, calcium levulinate 6.5 parts, houttuynine sodium bisulfite 2.5 parts, preservative 0.6 part, standby；
(2) being dissolved completely in normal saline by described temperature-sensitive hydrogel, the consumption of described normal saline is
8.5 times of the weight of described temperature-sensitive hydrogel, are then heated to 50 DEG C and keep after 17.5 minutes again
Put in 0 DEG C of frozen water and hatch until forming water white solution；
(3) by described biodegradable polymers disperse in deionized water, the consumption of described deionized water with
The concentration sum of described biodegradable polymers reaches 275g/L and is limited, and is added dropwise to the colourless of step (2)
Clear solution, add described D-phenylalanine derivant, glucokinase, Algin, Inonqqus obliquus,
Chitin derivativ, ellagic acid, linoleic acid, soybean oligo saccharide, anandamide, levulinic acid
Calcium, houttuynine sodium bisulfite, preservative, stirring, form mixed solution, ultrasonic reaction under normal pressure, room temperature
20min, at normal pressure, stands 6.5h at 12.5 DEG C, is evaporated to water content less than 42.5%, i.e. obtains institute
State spacetabs type hypoglycemic medicine composition；
(4) this spacetabs type hypoglycemic medicine composition will be proportionally added into adjuvant: the pregelatinized Starch of 15%, 2%
Hydroxymethyl cellulose, the hydrogenated vegetable oil etc. of 0.02%, by mixing, granulate, be dried, pelletize, tabletting
It is prepared as oral tablet etc. technique.
Embodiment 3:
A kind of spacetabs type hypoglycemic medicine composition, by weight, is mainly grouped by the one-tenth of following weight portion
Become: biodegradable polymers 200 parts, temperature-sensitive hydrogel 70 parts, D-phenylalanine derivant 10 parts,
Glucokinase 10 parts, Algin 12 parts, Inonqqus obliquus 20 parts, chitin derivativ 20 parts, tan flower
Acid 6 parts, linoleic acid 5 parts, soybean oligo saccharide 20 parts, anandamide 8 parts, calcium levulinate
10 parts, houttuynine sodium bisulfite 4 parts, preservative 1 part.
Wherein, described biodegradable polymers is the Polyethylene Glycol-glycolide-lactide copolymer that methylates.
The monomer molar ratio of the described Polyethylene Glycol-glycolide-lactide copolymer that methylates is in the range of 50: 20:
60, molecular weight is 50000 dalton, it is possible to can degrade voluntarily in physiological conditions, collapse or metabolism,
Medicine is made to keep suitable concentration and action time in vivo.Described temperature-sensitive hydrogel is poly(ethylene oxide),
Release medicine steady in a long-term, good biocompatibility can be reached, can degrade voluntarily.Described D-phenylalanine
Derivant is selected from Nateglinide, is a kind of novel blood sugar regulator used during user having meals, can effectively control post-prandial glycemia water
Flat, it is difficult to cause cardiovascular side effects, hypoglycemic incidence rate is relatively low.Described chitin derivativ is that shell is few
Sugar, to immunomodulating, antitumor, blood fat reducing, the regulation blood glucose of human body, improve liver and cardio-pulmonary function and
Other different physiological roles important roles.Described preservative is sodium benzoate, prevents medicine putrid and deteriorated,
Extend EDD, it is ensured that drug effect.
A kind of spacetabs type hypoglycemic medicine composition, its preparation method is:
(1) biodegradable polymers 200 parts, temperature-sensitive hydrogel 70 parts, D-benzene are taken by described proportioning
Alanine derivatives 10 parts, glucokinase 10 parts, Algin 12 parts, Inonqqus obliquus 20 parts, carapace
Element derivant 20 parts, ellagic acid 6 parts, linoleic acid 5 parts, soybean oligo saccharide 20 parts, arachidonic acid
Ethanolamine 8 parts, calcium levulinate 10 parts, houttuynine sodium bisulfite 4 parts, preservative 1 part, standby；
(2) being dissolved completely in normal saline by described temperature-sensitive hydrogel, the consumption of described normal saline is
11 times of the weight of described temperature-sensitive hydrogel, place into after being then heated to 50 DEG C of holdings 20 minutes
In 0 DEG C of frozen water, hatching is until forming water white solution；
(3) by described biodegradable polymers disperse in deionized water, the consumption of described deionized water with
The concentration sum of described biodegradable polymers reaches 450g/L and is limited, and is added dropwise to the colourless of step (2)
Clear solution, add described D-phenylalanine derivant, glucokinase, Algin, Inonqqus obliquus,
Chitin derivativ, ellagic acid, linoleic acid, soybean oligo saccharide, anandamide, levulinic acid
Calcium, houttuynine sodium bisulfite, preservative, stirring, form mixed solution, ultrasonic reaction under normal pressure, room temperature
30min, at normal pressure, stands 10h at 20 DEG C, is evaporated to water content less than 45%, i.e. obtains described slow
Release type hypoglycemic medicine composition；
(4) this spacetabs type hypoglycemic medicine composition will be proportionally added into adjuvant: the pregelatinized Starch of 15%, 2%
Hydroxymethyl cellulose, the hydrogenated vegetable oil etc. of 0.02%, by mixing, granulate, be dried, pelletize, tabletting
It is prepared as oral tablet etc. technique.
Drug release rate is measured:
By the tablet of this spacetabs type hypoglycemic medicine composition that embodiment 1, embodiment 2 prepare with embodiment 3
Using Chinese Pharmacopoeia dissolution detection method to measure release, condition is paddle method, and rotating speed is 50 revs/min, molten
Go out the phosphate buffer of 900 ml of ph 6.8 that medium is 37 DEG C.Embodiment 1, embodiment 2 are with real
The comparing result of the release executing example 3 is as follows, and table 1 is Nateglinide release, and table 2 is glucokinase
Release, table 3 is houttuynine sodium bisulfite release.
| Nateglinide release | 1h | 2h | 4h | 6h | 8h | 10h |
| Embodiment 1 | 6% | 21% | 38% | 62% | 81% | 98% |
| Embodiment 2 | 10% | 30% | 41% | 66% | 85% | 97% |
| Embodiment 3 | 12% | 34% | 45% | 71% | 88% | 99% |
Table 1
| Glucokinase release | 1h | 2h | 4h | 6h | 8h | 10h |
| Embodiment 1 | 8% | 14% | 32% | 61% | 87% | 97% |
| Embodiment 2 | 12% | 21% | 43% | 65% | 88% | 97% |
| Embodiment 3 | 20% | 36% | 64% | 72% | 91% | 98% |
Table 2
| Houttuynine sodium bisulfite release | 1h | 2h | 4h | 6h | 8h | 10h |
| Embodiment 1 | 3% | 18% | 34% | 57% | 79% | 91% |
| Embodiment 2 | 5% | 21% | 37% | 58% | 82% | 93% |
| Embodiment 3 | 10% | 27% | 41% | 61% | 86% | 98% |
Table 3
Above-mentioned dissolution release result shows: the present invention utilizes biodegradable polymers and temperature-sensitive hydrogel
Carry altogether with medicine, the purpose of the drug dissolution rates that reached to slow down, Drug controlled release, make medicine in vivo
Keep suitable concentration and action time, reduce access times and the dosage of medicine, long-term control blood glucose is had
Certain benefit.
Last it is noted that the foregoing is only the preferred embodiments of the present invention, it is not limited to
The present invention, although being described in detail the present invention with reference to previous embodiment, for the technology of this area
For personnel, the technical scheme described in foregoing embodiments still can be modified by it, or to it
Middle part technical characteristic carries out equivalent.All within the spirit and principles in the present invention, that is made any repaiies
Change, equivalent, improvement etc., should be included within the scope of the present invention.
Claims (8)
1. a spacetabs type hypoglycemic medicine composition, it is characterized in that, by weight, mainly it is composed of the following components in parts by weight: biodegradable polymers 80-200 part, temperature-sensitive hydrogel 30-70 part, D-phenylalanine derivant 3-10 part, glucokinase 2-10 part, Algin 5-12 part, Inonqqus obliquus 3-20 part, chitin derivativ 5-20 part, ellagic acid 1-6 part, linoleic acid 1-5 part, soybean oligo saccharide 5-20 part, anandamide 2-8 part, calcium levulinate 3-10 part, houttuynine sodium bisulfite 1-4 part, preservative 0.2-1 part.
2. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 1, it is characterised in that described biodegradable polymers is the Polyethylene Glycol-glycolide-lactide copolymer that methylates.
3. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 1, it is characterised in that described temperature-sensitive hydrogel is selected from poly(ethylene oxide) or poly(propylene oxide).
4. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 1, it is characterised in that described D-phenylalanine derivant is selected from Nateglinide.
5. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 1, it is characterised in that described preservative is sodium benzoate.
6. a kind of spacetabs type hypoglycemic medicine composition as described in claim 1-5 any one, it is characterised in that its preparation method is:
(1) biodegradable polymers 80-200 part, temperature-sensitive hydrogel 30-70 part, D-phenylalanine derivant 3-10 part, glucokinase 2-10 part, Algin 5-12 part, Inonqqus obliquus 3-20 part, chitin derivativ 5-20 part, ellagic acid 1-6 part, linoleic acid 1-5 part, soybean oligo saccharide 5-20 part, anandamide 2-8 part, calcium levulinate 3-10 part, houttuynine sodium bisulfite 1-4 part, preservative 0.2-1 part are taken by described proportioning, standby；
(2) described temperature-sensitive hydrogel is dissolved completely in normal saline, places in 0 DEG C of frozen water after being then heated to 50 DEG C of holdings 15-20 minute and hatch until forming water white solution；
(3) described biodegradable polymers is disperseed in deionized water, it is added dropwise to the colourless transparent solution of step (2), add described D-phenylalanine derivant, glucokinase, Algin, Inonqqus obliquus, chitin derivativ, ellagic acid, linoleic acid, soybean oligo saccharide, anandamide, calcium levulinate, houttuynine sodium bisulfite, preservative, stirring, form mixed solution, at normal pressure, ultrasonic reaction 10-30min under room temperature, at normal pressure, 3-10h is stood at 5-20 DEG C, it is evaporated to water content less than 40-45%, i.e. obtain described spacetabs type hypoglycemic medicine composition.
7. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 6 obtains preparation method, it is characterised in that the consumption of described normal saline is 6-11 times of the weight of described temperature-sensitive hydrogel.
8. a kind of spacetabs type hypoglycemic medicine composition as claimed in claim 6 obtains preparation method, it is characterised in that the consumption of described deionized water reaches 100-450g/L with the concentration sum of described biodegradable polymers and is limited.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1091004A (en) * | 1992-09-18 | 1994-08-24 | 山之内制药株式会社 | Hydrogel slow-releasing agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1091004A (en) * | 1992-09-18 | 1994-08-24 | 山之内制药株式会社 | Hydrogel slow-releasing agent |
Non-Patent Citations (2)
| Title |
|---|
| 任国飞: "那格列奈新剂型研究进展", 《中国药业》 * |
| 杨桔: "PLGA微球/P（NIPAAm-co-AAm）水凝胶复合体系的构建及药物缓释性能研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
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